This research aims to study mechanisms of synaptic function with emphasis on the origins and locations of individual synaptic membrane polypeptides. By reacting epsilon-amino groups of lysines which are exposed on membrane surfaces with sodium boro(3H)hydride in the presence of pyridoxal phosphate it is possible to selectively label exposed peptide areas of intact synaptosomal membranes. Combining this technique with purification and subsequent gel electrophoresis of synaptosomal subfractions from chick brain allows classification of membrane polypeptides into four groups: those occurring entirely within the membrane, those exposed on both the internal and external faces, and those exposed only at one surface, either external or internal. The nature of the peptides around the exposed lysine residues will be characterized by labeling polypeptides eluted from the gels with 125I, cleaving with trypsin or cyanogen bromide, and performing autoradiographic peptide mapping on the resulting peptide mixtures. Whether or not synaptic vesicles fuse with the external membrane will be investigated by comparing labeled gels and peptides of these two fractions. Distances between polypeptides in the membrane will be determined with bifunctional reagents with various bridge lengths between the functional groups. When basic parameters are defined synaptosomes prepared from synapses in differing states of activity will be examined. Alterations of membrane conformation and subsequent protein exposure may reflect neural activity.